Analysis of HLA-ABC locus-specific transcription in normal tissues

Analysis of HLA-ABC locus-specific transcription in normal tissues
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DOI:
10.1007/s00251-010-0470-z
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发表时间:
2010-12-01
期刊:
影响因子:
3.2
通讯作者:
Garrido, Federico
Garrido, Federico
中科院分区:
医学4区
文献类型:
--
作者:
Belen Garcia-Ruano, Ana;Mendez, Rosa;Garrido, Federico

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我们开发了一种新的人类白细胞抗原HLA-ABC位点特异性定量实时聚合酶链反应(PCR),以确定位点特异性基因表达的HLA-ABC在外周血白细胞(PBLs,n = 53),结肠粘膜(n = 15),喉粘膜(n = 15)。激光辅助组织显微切割使我们能够在不受周围基质干扰的情况下研究所选细胞。我们报告的证据的特异性的技术,描述的HLA-ABC位点特异性的基因表达模式中发现的PBL和两个实体组织的研究。PBL显示HLA-B的基因表达高于HLA-A或HLA-C(分别为p = 4.7 x 10(-10)和p = 1.6 x 10(-6))。在实体组织中,HLA-A和HLA-B基因表达相似,HLA-C表达较低。特别是在喉粘膜中,发现HLA-A和HLA-C表达之间以及HLA-B和HLA-C表达之间存在显著差异(分别为p = 6.5 x 10(-4)和p = 8.1 x 10(-4))。在结肠粘膜中观察到相同的差异,但未达到显著性(分别为p = 0.08和p = 0.06)。位点特异性调节的差异可能与NK和CD 8阳性T细胞的细胞毒性应答的控制有关。HLA-ABC特异位点的基因表达无个体内变异,但个体间变异较大。这可能是由于控制HLA-ABC组成型表达的共同调节因子的表达差异所致。
We developed a novel human leukocyte antigen HLA-ABC locus-specific quantitative real-time polymerase chain reaction (PCR) to determine the locus-specific gene expression of HLA-ABC in peripheral blood leukocytes (PBLs, n = 53), colon mucosa (n = 15), and larynx mucosa (n = 15). Laser-assisted tissue microdissection allowed us to study the selected cells without interference from surrounding stroma. We report evidence on the specificity of the technique, describing the HLA-ABC locus-specific gene expression patterns found in the PBLs and two solid tissues studied. PBLs showed a higher gene expression of HLA-B than of HLA-A or HLA-C (p = 4.7 x 10(-10) and p = 1.6 x 10(-6), respectively). In solid tissue, HLA-A and HLA-B gene expressions were similar and HLA-C expression lower. In particular, in larynx mucosa, significant differences were found between HLA-A and HLA-C expressions and between HLA-B and HLA-C expressions (p = 6.5 x 10(-4) and p = 8.1 x 10(-4), respectively). The same differences were observed in colon mucosa, but significance was not reached (p = 0.08 and p = 0.06, respectively). Differences in locus-specific regulation may be related to the control of cytotoxic responses of NK and CD8 positive T cells. Gene expression of HLA-ABC specific locus showed no intra-individual variability, but there was a high inter-individual variability. This may result from differences in the expression of common regulatory factors that control HLA-ABC constitutive expression.